The development of new probes, homogeneous assays, and miniaturized devices that allow for the direction detection of compounds or specific binding events is having an impact in basic research, clinical diagnostics, and drug development. Novel fluorescent and luminescent technologies are especially important for the implementation of greater speed and automation. These advances are being applied to the detection, localization of gene sequences, proteins, infectious organisms, and a variety of other targets. The primary goal of this proposal is to develop a new class of biological detection labels by conjugating biological molecules to semiconductor quantum dots (nanocrystals). The quantum dots are detected by their intense photoluminescence, and the attached biomolecules recognize specific analytes such as proteins, DNA, or viruses. Recent research in our group has developed a simple procedure that allows highly luminescent quantum dots (ZnS-capped CdSe) to be solubilized in water; the water-soluble quantum dots are biocompatible and can bo covalently linked to large biomolecules (SCIENCE 281, 2106-2018, 1998). In comparison with organic dyes, this new class of luminesc3nt labels offers significant advantages such as size-tunable emission wavelength, symmetric spectral shapes, and simultaneous excitation at a single wavelength. The primary goal os this proposal is to develop a new class of biological detection by conjugating biological molecules to semiconductor quantum dots (nanocrystals). The quantum dots are detected by their intense photoluminescence, and the attached biomolecules recognize specific analytes such as proteins, DNA, or viruses. Recent research in our group has developed a simple procedure that allows highly luminescent quantum dots (ZnS-capped CdSe) to be solubilized in water; the water- soluble quantum dots are biocompatible and can be covalently linked to large biomolecules (SCIENCE 281, 2106-2018, 1998). In comparison with organic dyes, this new class of luminescent labels offers significant advantages such as size-tunable emission wavelength,, symmetric spectral shapes, and simultaneous excitation at a single wavelength. The proposed research will systematically examine a variety of quantum dot bioconjugates for biological and biomedical applications. The basic materials will include group II-VI (Cds and CdSe) and group III-V (InP and InAs) semiconductors, with emission wavelengths tunable from the blue to the near infrared. An inorganic capping layer will be used to improve the photostability and luminescence quantum yields. The capped quantum dots will be conjugated to two broad categories of biological molecules-proteins and nucleic acids. Strategies will also be developed to manipulate the quantum dot optical properties, such as the quenching of quantum dot luminescence with organic chromophores. Quantum dot bioconjugates are expected to be available in large quantities and in lyphophilized forms, for broad distribution to the scientific community.